丁苯酞对糖尿病小鼠认知功能障碍及海马N-甲基-D-天冬氨酸受体表达的影响  

Effect of L-3-n-butylphthalide on cognitive impairment and expression of N-methyl-D-aspartate receptors in hippocampus of diabetic mice

作　　者：王海芳[1] 张钢[1] 张彦春[2] 董运强[3] 赵娜 兰敏 冀素晓 张松筠[4] 

机构地区：[1]邯郸市第一医院内分泌科,056000 [2]邯郸市中心医院分院内分泌科 [3]邯郸市疾病预防控制中心 [4]河北医科大学第二医院内分泌科

出　　处：《中华老年心脑血管病杂志》2017年第11期1199-1202,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：邯郸市科学技术研究与发展计划(1623208064)

摘　　要：目的观察丁苯酞对2型糖尿病db/db小鼠学习记忆及海马N-甲基-D-天冬氨酸(NMDA)受体表达的影响,并探讨其机制。方法将16只雄性C57BL/KsJ-db/db小鼠按随机数字表法分为丁苯酞干预组[L-NBP组,予以120mg/(kg·d)丁苯酞灌胃,8只]和糖尿病对照组(DM组,等量植物油灌胃,8只),同窝出生的db/m小鼠作为正常对照组(NC组,等量植物油灌胃,10只)。干预6周后,进行指标观察。应用Morris水迷宫检测小鼠的学习记忆能力,电生理实验记录小鼠体内海马前穿通纤维-齿状回通路长时程增强(LTP)的变化,RT-PCR检测NMDA受体亚单位(NR2B)mRNA表达情况。结果与NC组比较,DM组小鼠平均逃避潜伏期延长和穿越平台次数减少(P<0.05),L-NBP组小鼠上述学习记忆成绩明显改善(P<0.05);与NC组比较,DM组和L-NBP组小鼠海马LTP明显降低[(136.17±12.73)%、(174.17±20.35)%vs(251.67±43.78)%,P<0.05],海马CA1区NR2B mRNA表达水平明显下降(1.02±0.12、1.42±0.12 vs 1.86±0.14,P<0.05)。结论丁苯酞可能通过上调糖尿病小鼠海马CA1区NMDA受体的表达,促进LTP,改善糖尿病小鼠学习记忆能力。Objective To study the effect of L-3-n-butylphthalide（L-NBP）on learning,memory and expression of N-methyl-D-aspartate（NMDA）receptor in hippocampus of diabetic mice.Methods Sixteen diabetic mice were divided into L-NBP group（n=8）and DM group（n=8）with 10 littermate db/m mice served as a control group.Six weeks after the animals in L-NBP group were given L-NBP and those in DM group and control group were given vegetable oil by oral gavage.The long-term potentiation（LTP）in hippocampus was recorded during the electrophysiological experiments.The expression of NMDA receptor subunit NR2 BmRNA was detected by RT-PCR.Results The escaping latency time was longer,the average number of cross platform explorations was smaller in DM group than in control group（P〈0.05）.The learning and memory scores were significantly higher in L-NBP group than in DM group（P〈0.05）.The LTP in hippocampus and the expression level of NR2 B mRNA in hippocampal CA1 area were significantly lower in DM group and L-NBP group than in control group（136.17% ±12.73%,174.17% ±20.35% vs251.67%±43.78%,P〈0.05;1.02±0.12,1.42±0.12 vs 1.86±0.14,P〈0.05）.ConclusionL-NBP improves the leaming and memory of diabetic mice by upregulating the expression of NMDA receptor and LTP in their hippocampal CA1 area.

关 键 词：糖尿病 认知障碍 受体 N-甲基-D-天冬氨酸 长时程增强 记忆 丁苯酞 

分 类 号：R587.2[医药卫生—内分泌] R747.9[医药卫生—内科学]